36 replies to this topic

[Michael]

All:

 

This thread has gone in several directions, but there are a fair number of posts that are specific to questions around CMV, anergic T-cells, and thymic rejuvenation, centered around critiquing or defending Dr. de Grey's and/or SENS Research Foundation's views and proposals on these subjects. The subthread is distinct enough that I've moved it to its own thread. It's going to take me a while to disentangle all of this, but I will weigh in to clarify several points and (yes) offer a scientific argument for why we're doing what we're (actually) doing.

[Antonio2014]

Michael, have you (and Aubrey) seriously considered to release "Ending Aging" under a free license? I see time and again people criticizing SENS strategy without knowing its details, and I think making the book open access (like the SENS website or this forum) would eliminate much of the misunderstanding. Are the book's royalties so high that they justify maintaining it as non-freely available?

Edited by Antonio2014, 24 June 2015 - 11:11 AM.

[Michael]

If you're the same "Antonio" with whom I've had this discussion twice before, you already know that we have . As I've said previously, it's not actually up to us: the publisher turns over royalties to us, but they set the prices and do the distribution, and, well, they're a  for-profit publishing company and not a public education charity. The Foundation does give many copies away every year, often to donors or at conferences; in these cases, we buy them from the publisher.

 

But also, books are so cheap these days that I'd be very surprised if more than a handful of citizens in a developed economy who was actually motivated to read the book would be unwilling to shell out the two-Starbucks Grandes worth of money involved. Heck, Amazon has used copies of the hardcover for $2.75 + $3.99 shipping. I have no data to research this, but I have to imagine that the folks who haven't read the book have not yet been moved to do so, for lack of time or for feeling that they don't need a lot of detail.

[Antonio2014]

Yes, I'm the same Antonio    but I found the previous answer (I only remember one) too short (it was buried inside a long reply) and I didn't want to engage in a discussion then.

 

But also, books are so cheap these days that I'd be very surprised if more than a handful of citizens in a developed economy who was actually motivated to read the book would be unwilling to shell out the two-Starbucks Grandes worth of money involved.

 

The problem is, people that criticize SENS, or aren't convinced by SENS, or simply don't know SENS will not buy the book. So the people most in need of a detailed explanation will not read it. Only people already convinced buy the book. It's even worse, convinced people can't cite parts of the book to explain the misunderstandings of the critics.

 

Also, outside the US it isn't so cheap at all. The Spanish version costs around $18 + shipping costs in Amazon (probably much more in a physical shop). Few people will pay $25-30 to read about a theory/research they know little or nothing about, that don't appear on TV/newspapers, and that promises too-good-to-be-true results (indefinite lifespans).

 

I see the same problem in other projects, like The Mars Society's Mars Direct project. They have a book, but time and time again people write criticisms that are already refuted in the book. They simply didn't read it and will not read it, and the project supporters have to painfully write the same old, long replies ad nauseam.

 

Anyway, if you aren't the copyright owners anymore, there is nothing to do, that's true. Thanks for your reply

Edited by Antonio2014, 25 June 2015 - 09:43 AM.

[Michael]

The promised discussion of this study is now up on the SENS Research Foundation website, as Newsletter Question of the Month #11: Are Mitochondrial Mutations Really All That Important?

[Lebombo]

Extension of Cell Life-Span and Telomere Length in Animals Cloned from Senescent Somatic Cells

 

http://www.columbia....ence288_665.pdf

 

 

Robert Lanza and his previous team were the first to perform this research and demonstrate the process back in 2000.

Edited by Lebombo, 10 September 2015 - 07:58 AM.

[Avatar of Horus]

In this topic I have posted a result about the genetic control of aging damage in the mitochondria:

Study Suggests Role of CISD2 Gene in Aging
http://www.longecity...-gene-in-aging/
 

... 
It seems it has some role in normal aging too:
 

Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice
Chen et al. Genes Dev. 2009
http://www.ncbi.nlm....pubmed/19451219
Abstract
CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, the CISD2 gene is located on human chromosome 4q, where a genetic component for longevity maps. Here we show for the first time that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial degeneration appears to have a direct phenotypic consequence that triggers the accelerated aging process in Cisd2 knockout mice; furthermore, mitochondrial degeneration exacerbates with age, and the autophagy increases in parallel to the development of the premature aging phenotype. ...

Cisd2 mediates mitochondrial integrity and life span in mammals
Chen et al. 2009
http://www.ncbi.nlm....pubmed/19717971
Abstract
CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Using a mouse genetic approach, this work demonstrated for the first time that Cisd2 is involved in mammalian life span control. Cisd2 deficiency in mice leads to mitochondrial breakdown and dysfunction; this is accompanied by cell death with autophagic features and these events precede the two earliest manifestations of nerve and muscle degeneration. Together, they lead to a panel of phenotypic features suggestive of premature aging. This work effectively links Cisd2 gene function, mitochondrial integrity and aging in mammals.

A persistent level of Cisd2 extends healthy lifespan and delays aging in mice
Wu et al. 2012
http://www.ncbi.nlm....pubmed/22661501
Abstract
The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging. In this study, we demonstrate that a persistent level of Cisd2 achieved by transgenic expression in mice extends their median and maximum lifespan without any apparent deleterious side effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. These results suggest that Cisd2 is a fundamentally important regulator of lifespan and provide an experimental basis for exploring the candidacy of CISD2 in human longevity.

 
some details from the full text:
http://hmg.oxfordjou...21/18/3956.long

...
Cisd2 protects mitochondria from age-associated damage, reduces the age-associated declines in mitochondrial function and whole-body energy metabolism

Since Cisd2 deficiency causes mitochondrial dysfunction and triggers an accelerated aging process in Cisd2 KO mice, we sought to investigate whether an elevated level of the Cisd2 protein was able to protect mitochondria from age-associated damage in Cisd2 TG mice. There is progressive damage to mitochondrial DNA (mtDNA) during aging. To study whether Cisd2 is able to protect mitochondria from age-associated genomic damage, we examined mtDNA integrity by long polymerase chain reaction (PCR; 13.6 kb) of mtDNA (23) ...
Indeed, we detected a reduction in the amplification of the 13.6-kb fragment and an increase in the number of shorter PCR fragments in the old (24-mo) WT mice compared with the young (3-mo) mice (Fig. 5B and C). In contrast, the old (24-mo) Cisd2 TG mice were protected from this age-associated increase in mtDNA damage (Fig. 5B and C).

To investigate whether an attenuation of the age-associated damage to mtDNA has a direct functional benefit, we assessed aerobic respiration using isolated mitochondria prepared from skeletal muscle. Our results revealed an age-dependent decrease in oxygen consumption in both the WT and Cisd2 TG mice; however, there was a remarkable increase in the oxygen consumption of the mitochondria from the Cisd2 TG mice compared with those from the WT controls at the old age (24-mo) (Fig. 5F). ...
Together, these results show that constitutive expression of Cisd2 protects mitochondria and reduces the age-associated decline in aerobic respiration during aging.

To assess the impact of better preserved mitochondrial function on age-associated changes in whole-body energy metabolism, we monitored the mice by indirect calorimetry. Consistent with the decreased oxygen consumption observed using the isolated mitochondria of old (24-mo) WT mice, whole-body oxygen consumption (VO2), CO2 production (VCO2) and heat generation were significantly decreased in the old (24-mo) WT mice compared with the young (3-mo) WT mice during both light and dark cycles (Fig. 6A–F). In contrast, old (24-mo) Cisd2 TG mice were well protected from these age-associated reductions in O2 consumption, CO2 production and heat generation during the light cycle; furthermore, during the dark cycle, although the reduction in these age-associated parameters was not fully protected, the decline was significantly attenuated in the Cisd2 TG mice (Fig. 6D–F). Taken together, these results demonstrate that aging is associated with mitochondrial damage and is accompanied by a reduction in mitochondrial function and whole-body energy metabolism. Importantly, these deleterious changes can be prevented or significantly ameliorated by a persistent level of Cisd2 expression during aging.
...